This invention is generally in the field of capillary electrophoresis, and relates particularly to a system for and a method of processing the signals of a photodetector array of a multiplexed or xe2x80x9cparallelxe2x80x9d capillary electrophoresis system.
Capillary electrophoresis (CE) is a chemical separation technique involving the use of one or more capillary tubes.
Parallel CE, a recently developed technique using many parallel capillary tubes, is growing in popularity since this technology allows multiple samples to be analyzed quickly and efficiently. This is particularly advantageous in combinatorial chemistry where many hundreds and even thousands of samples are analyzed over a short period of time. Parallel CE involves the use of a xe2x80x9cbundle xe2x80x9d of capillary tubes, e.g., 96 such tubes. A chemical sample to be analyzed is loaded in each tube, and a high voltage is applied to the tube, causing the components of the sample to migrate in the tube at different speeds, thereby causing separation of the components which can then be analyzed by conventional light absorption or other techniques. For example, a photodetector array of linear elements may be used to sense the light passing through the bundle. Reference may be made to the following patents and publications for a more detailed description of CE, including parallel CE, and various analytical techniques used in CE: U.S. Pat. Nos. 5,900,934, 5,324,401, 5,312,535, 5,303,021, 5,239,360; C. Culbertson et al., Analytical Chemistry, 70, 2629-2638 (1998); and X. Gong et al., Analytical Chemistry, 7.2, A-H (1999).
The signals generated by elements of the photodetector array represent the separation of the components. Some of the signals represent light passing through the walls of the capillary tubes while other signals represent light passing between the capillary tubes and yet other signals represent light passing through the center of the capillary tubes. Some of these signals include more accurate information indicative of the separation of the components. In addition, the signals are subject to noise. There is a need for a system which processes signals to maximize the accuracy of the information embodied in the signals.
Among the several objects of this invention may be noted the provision of apparatus and method for optimizing the results of a capillary electrophoresis operation, particularly the clarity, resolution and/or detection limits of electropherograms generated during the operation; the provision of such an apparatus and method which average signals generated by elements of the array; the provision of such an apparatus and method which minimize long time drifts of signals generated by the elements of the array to generate a substantially flat baseline of the signals and which minimize short time fluctuations or other noise of such signals to generate an improved signal to noise ratio of the output signals; the provision of such apparatus and method which involve the use of conventional components for reduced cost; and the provision of such apparatus and method which are quick and easy to use.
In one form, the invention comprises a parallel capillary electrophoresis system for separating and analyzing the components of multiple chemical samples. A bundle of capillary tubes is arrayed to have at least portions of the tubes extending generally parallel to one another in a first plane. Each tube is adapted for the flow of a fluid sample therethrough. A power source applies a potential difference between inlet end portions and outlet end portions of the tubes to cause an electrical current to flow through the contents of the capillary tubes at a level sufficient to cause separation in the fluid samples. A light source emits light which passes through the capillary tube portions. A photodetector comprising a linear array of photodetector elements receives light passing through the capillary tubes, the light passing through each the capillary tube portions illuminating several photodetector elements. Each the photodetector element generates a pixel signal corresponding to the light received by the photodetector element. An analog to digital converter converts each of the pixel signals into a digital value corresponding to the light received by one of the photodetector elements. The improvement comprises a processor receiving the digital values and generating a plurality of output signals corresponding thereto. Each output signal is a function of at least two digital values corresponding to the light received by two photodetector elements, respectively, so that the output signals correspond to the light passing through the bundle of capillary tubes.
In another form, the invention comprises a method of processing a plurality of pixel signals, each generated by one element of an array of photodetector elements illuminated by light passing through a bundle of capillary tubes during a multiplexed capillary electrophoresis process. The method comprises the steps of:
converting each of the pixel elements signals into a digital value corresponding to the light received by one of the photodetector elements;
selecting, for each capillary tube, at least two digital values corresponding to the light received by two photodetector elements; and
generating output signals corresponding to the light passing through the bundle of capillary tubes, each output signal being a function of the selected digital values.
Other objects and features will be in part apparent and in part pointed out hereinafter.